Browsing by Author "Cormode, David P."

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    Ferumoxytol Nanoparticles Target Biofilms Causing Tooth Decay in the Human Mouth
    (American Chemical Society, 2021) Liu, Yuan; Huang, Yue; Kim, Dongyeop; Ren, Zhi; Oh, Min Jun; Cormode, David P.; Hara, Anderson T.; Zero, Domenick T.; Koo, Hyun; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Severe tooth decay has been associated with iron deficiency anemia that disproportionally burdens susceptible populations. Current modalities are insufficient in severe cases where pathogenic dental biofilms rapidly accumulate, requiring new antibiofilm approaches. Here, we show that ferumoxytol, a Food and Drug Administration-approved nanoparticle formulation for treating iron deficiency, exerts an alternative therapeutic activity via the catalytic activation of hydrogen peroxide, which targets bacterial pathogens in biofilms and suppresses tooth enamel decay in an intraoral human disease model. Data reveal the potent antimicrobial specificity of ferumoxytol iron oxide nanoparticles (FerIONP) against biofilms harboring Streptococcus mutans via preferential binding that promotes bacterial killing through in situ free-radical generation. Further analysis indicates that the targeting mechanism involves interactions of FerIONP with pathogen-specific glucan-binding proteins, which have a minimal effect on commensal streptococci. In addition, we demonstrate that FerIONP can detect pathogenic biofilms on natural teeth via a facile colorimetric reaction. Our findings provide clinical evidence and the theranostic potential of catalytic nanoparticles as a targeted anti-infective nanomedicine.
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    Topical ferumoxytol nanoparticles disrupt biofilms and prevent tooth decay in vivo via intrinsic catalytic activity
    (Springer Nature, 2018-07-31) Liu, Yuan; Naha, Pratap C.; Hwang, Geelsu; Kim, Dongyeop; Huang, Yue; Simon-Soro, Aurea; Jung, Hoi-In; Ren, Zhi; Li, Yong; Gubara, Sarah; Alawi, Faizan; Zero, Domenick; Hara, Anderson T.; Cormode, David P.; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Ferumoxytol is a nanoparticle formulation approved by the U.S. Food and Drug Administration for systemic use to treat iron deficiency. Here, we show that, in addition, ferumoxytol disrupts intractable oral biofilms and prevents tooth decay (dental caries) via intrinsic peroxidase-like activity. Ferumoxytol binds within the biofilm ultrastructure and generates free radicals from hydrogen peroxide (H2O2), causing in situ bacterial death via cell membrane disruption and extracellular polymeric substances matrix degradation. In combination with low concentrations of H2O2, ferumoxytol inhibits biofilm accumulation on natural teeth in a human-derived ex vivo biofilm model, and prevents acid damage of the mineralized tissue. Topical oral treatment with ferumoxytol and H2O2 suppresses the development of dental caries in vivo, preventing the onset of severe tooth decay (cavities) in a rodent model of the disease. Microbiome and histological analyses show no adverse effects on oral microbiota diversity, and gingival and mucosal tissues. Our results reveal a new biomedical application for ferumoxytol as topical treatment of a prevalent and costly biofilm-induced oral disease.